The evidence supporting the comprehensive benefits of the new anti-viral regimens for treatment of hepatitis C infection

In 2018, there is substantial evidence that hepatitis C virus (HCV) infection is a systemic disease associated with adverse clinical, economic, and patient-reported outcomes (PROs). Specifically, the clinical consequences of HCV infection can lead to both hepatic and extrahepatic manifestations. In this context, HCV infection increases the risk of liver-related and overall mortality. Additionally, HCV infection can also negatively influence patient-reported outcomes as documented by severe impairment of healthrelated quality of life and lower worker productivity. Finally, there is substantial evidence that HCV infection is responsible for enormous economic burden related to the direct, indirect, and intangible costs of HCV infection to the individuals and the society.1

It is also important to recognize that eradicating HCV and achieving sustained virologic response (SVR, a surrogate marker for HCV cure with survival benefit) can improve clinical outcomes, economic outcomes, and patient-reported outcomes. Although, long-term post-SVR data have substantiated the benefit of SVR using the old regimens, there have been questions raised about the long-term benefits of the new all oral, interferon free direct-acting antiviral agents (DAAs) for treatment of HCV infection. In fact, a systematic review published by the Cochrane group raised concern about the true long-term benefits of the new DAA regimens. In the context of the conclusions of this meta- analysis, one must assess recent evidence supporting the benefits of SVR with DAAs and examine a number of issues with the Cochrane Review.2

It is also important to emphasize increasing evidence supporting the benefit of SVR with the new anti-HCV regimens. In a recent large study, patients who achieved SVR with either interferon or DAA containing regimens experienced significant reductions in both liver and non-liver complications and mortality. Data specifically related to the benefits of DAAs came from another systematic review and metaanalysis published in the Annals of Internal Medicine in 2017 which included 42 studies of FDA-approved DAA regimens. This study concluded that the majority of DAA regimens demonstrated great success as evidenced by their high rates of SVR. This data was further supported by another study which clearly showed the benefit of DAAs by improving the hepatic function of the liver transplant candidates with HCV leading to the delisting of these patients. In multiple other studies which were presented at the international scientific meetings in 2017, achieving SVR with the DAAs was shown to lead to a reduction in the hepatic complications in patients with HCV-related cirrhosis.

There is also substantial data that achievement of SVR with DAAs can lead to a reduction in the cardio-vascular manifestations of HCV infection as well as a significant reduction in the risk of HCC. Finally, SVR with DAA has been shown to improve patients’ survival. In fact, a study using data from Electronically Retrieved Cohort of HCV Infected Veterans, documented the mortality benefit of those HCV infected patients who were treated with DAAs.3 Furthermore, a large prospective analysis of data from the Therapeutic Option For Hepatitis B and C: A French Nationwide Cohort Study, provides additional support of improvement in survival of patients with HCV infection who achieved SVR with DAA treatment.4

In addition to the clinical benefits achieved with DAA’s, there is also substantial evidence that achieving SVR with DAAs can lead to improvement of PROs such as health-related quality of life (HRQL) and worker productivity. Finally, these regimens have been shown to be cost-effective in the United States and other Western countries and can bring value to the patient and the society.1


Increasing evidence supports the benefit of SVR with the new anti-HCV regimens.


In the context of this substantial mounting evidence, it is necessary to re-examine the Cochrane Review’s conclusions. Furthermore, it is important to note some methodologic flaws with this review. In fact, a number of the studies included in the Cochrane Review were nonrelevant since these regimens had previously been shown to be ineffective or unsafe and could not be used in clinical practice. This is in contrast to the previously mentioned systematic review which only focused on FDA approved, clinically relevant regimens.2 Another flaw of the Cochrane analysis was to ignore the impact of DAA regimens on HRQL and patient reported outcomes, an important outcome of increasing importance to the FDA and Medicare.1,2

In summary, the current evidence supports the high-efficacy and the safety of the approved DAA regimens for treatment of chronic HCV infection.1-4 In fact, these efficacy data coupled with the PRO evidence indicate that treatment of HCV with the new DAAs not only lead to high SVR rates but also to an improvement in survival and patient-reported outcomes and to a reduction in the future economic burden of HCV infection. Therefore, HCV cure by the new regimens provides comprehensive benefits not only to patients but also to the entire society.1

Dr. Younossi has received research support from Intercept, Gilead and BMS.

References
1. Younossi, Z.M., Birerdinc, A., Henry, L. Hepatitis C infection: A multifaceted systemic disease with clinical, patient reported and economic consequences. J Hepatol. 2016;65:S109-19.
2. European Association for the Study of Liver. Response to the Cochrane systematic review on DAA-based treatment of chronic hepatitis C. J Hepatol. 2017;67:663-664.
3. Butt, A.A., Yan, P., Simon, T.G., Abou-Samra, A.B. Effect of paritaprevir/ritonavir/ombitasvir/dasabuvir and ledipasvir/sofosbuvir regimens on survival compared with untreated hepatitis C virus–infected persons: Results from ERCHIVES. Clin Infect Dis. 2017;65:1006-1011.
4. The ANRS-AFEF Hepather Study Group. First Prospective evidence of decreased mortality after direct acting antivirals in the French ANRS CO22 HEPATHER cohort. AASLD. 2017.

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